Ultrastructure of Pituitary Tumor Cells: A Critical Study

Olivier, L; Vila-Porcile, Évelyne; Racadot, O; Peillon, F; Racadot, J

doi:10.1016/b978-0-12-692050-5.50014-0

Cited by 30 publications

(10 citation statements)

References 111 publications

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“…The granules in the present neoplasm are consistent in size, form and density with those previously observed in ACTH-secreting pituitary tumours (Olivier et al, 1975). Observations on granule size and character in cases with 'ectopic' ACTH-producing tumours are too few to permit comparison with the present case, although an ACTH-producing islet cell tumour of the pancreas (Rawlinson, 1973) exhibited many of the submicroscopic features, including secretory granules, usually observed with pituitary ACTH-producing tumours.…”

Section: Discussionsupporting

confidence: 85%

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

Krienger

Choi

Anderson

1976

Clinical Endocrinology

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The nature of ACTH present in pituitary tumours associated with Cushing's disease has not been previously characterized nor correlated with the electron microscopic appearance. The present report describes the culture of tumour tissue obtained from a patient with a pituitary tumour associated with Cushing's disease, and the characterization of the ACTH content of tumour and media by bioassay, immunoassay, and Sephadex G-50 gel filtration. Electron microscopic studies were also performed. The pathological diagnosis was pituitary adenoma with basophilic PAS-positive granules. Electron microscopy showed uniformity of size and shape of the tumour cells, the presence of secretory granules of varying size and density, and disorganized tubular and vacuolar arrays of endoplasmic reticulum. The bioreactive ACTH content of the tumour was 0-29 mug/g, which is markedly below that seen in the normal pituitary, but within the range reported for ectopic ACTH-producing tumours. Immunoreactive ACTH when measured by a C-terminal antibody was five-fold higher than when measured by an N-terminal antibody; the latter gave a value of 1-24 mjg/g. On Sephadex G-50 gel filtration, 9% of the N-terminal immunoreactivity was present in the Vo fraction ('big' ACTH). This latter fraction had a greater percentage of bioreactivity (28%) than previously reported for this molecular species. Analysis of the tumour culture medium revealed a variation in molecular size similar to that seen in the tumour, although the percentage of ACTH of large molecular size was greater, suggesting increased secretion of a possible 'prohormone' by the tumour. Plasma ACTH was characterized by a 2:1 ratio of immunoreactivity (N-terminal) to bioreactivity, and a 4:1 ratio of C-terminal/N-terminal immunoreactivity. This report also appears to be the first of successful short-term tissue culture of a primary ACTH-producing tumour. The granule size was considerably larger than that reported for normal pituitary ACTH-containing cells.

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Section: Discussionsupporting

confidence: 85%

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

Krienger

Choi

Anderson

1976

Clinical Endocrinology

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“…2b). SRI I nduced granule reduction has been reported [20]. An in crease of lysosomal activity was not observed [23], but ibis latter discrepancy may be explained by the fact that we ex amined cells minutes after exposure to SRIF, whereas the comparable observation in the conflicting report was not made until 1 -4 h later [23], by which time lysosomal activity may have normalized (table III).…”

Section: Discussioncontrasting

confidence: 43%

Structural Correlates of Stimulated and Inhibited Secretion: Electron Microscopic Observations of Somatotrophs in Perifused Rat Pituitary

Stachura

Costoff

Tyler³

1986

Neuroendocrinology

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The in vitro release of stored intracellular rat growth hormone (rGH) in response to several secretagogues suggests the functional division of rGH storage into at least two ‘compartments’ or ‘pools’. The first is an immediately releasable compartment whose response is brief. The second is a compartment which responds to more prolonged secretory demands. These observations are consistent with either a single, homogeneous population of somatotrophs, each of which exhibits functional compartmentalization of storage, or with heterogeneous populations of somatotrophs, each family of which provides one of the observed responses. We sought anatomical correlates of this functional compartmentalization using a perifusion/morphometric system which permitted examination of the first model while not excluding the second model. We selected for study an established perifusion protocol whose behavior was consistent and whose previous results suggested phases of both filling and emptying of the immediate release pool. Five parallel perifusions of pituitary fragments were run. The fifth perifusion was used to monitor rGH release and to confirm that the experiment had behaved in standard fashion. The first pituitary chamber was dismantled during basal perifusion to obtain tissue for microscopy, the next during exposure to 25 nM SRIF, the third during exposure to both 25 nM SRIF and 1 mM (Bu)₂cAMP, and the fourth shortly after the rapid release which followed SRIF withdrawal. Somatotroph granulation was decreased by 54% in the presence of SRIF, and then increased by 45% with the addition of (Bu)₂cAMP. The intracellular distribution of granules also fluctuated in relation to the stimulatory and inhibitory secretagogues. In addition, secondary lysosomes increased by 549% during SRIF-induced inhibition of rGH release. Cell volume was decreased by 37% in the presence of 25 nM SRIF; the addition of (Bu)₂cAMP did not reverse this SRIF effect. We conclude that the in vitro release phenomenon we have termed the ‘immediate release pool’ has an anatomic correlate in juxtamembrane granules, that inhibition of rGH release is accompanied by a significant increase in secondary lysosome activity, that while heterogeneous populations of somatotrophs probably exist, individual cells possess a range of responses consistent with functional compartmentalization, and that rGH release involves not only granule movement between anatomically demonstrable compartments, but in addition, major and rapid changes in somatotroph volume.

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“…The ultrastructure of the GH, cells in response to secretagogues has been examined by various groups (Gourdji et al, 1972;Olivier et al, 1975;Tixier-Vidal, 1975;Tougard et al, 1982) (Figs. 12, 13) (Table 3).…”

Section: Ultrastructural Studies Of Cultured Pituitary Tumorsmentioning

confidence: 99%

“…The development of spontaneous pituitary tumors has been described in many species of animals, al-though these tumors have been studied most extensively in the rat and mouse. Spontaneous anterior pituitary tumors have been described in fish, parakeets, buffalo, cows, dogs, horses, humans as well as rats and mice (Beech, 1981;Costoff, 1973;El Eltreby et al, 1977;Gardner et al, 1953;Kovacs and Horvath, 1986;Liebelt, 1979;Olivier et al, 1975). Schlumberger (1956) described three spontaneous pituitary tumors in parakeets which were used to establish transplantable strains.…”

Section: Spontaneous Tumorsmentioning

confidence: 99%

Ultrastructure of spontaneous and transplanted pituitary tumors in laboratory animals

Lloyd

1991

J. Elec. Microsc. Tech.

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The present review examines ultrastructural studies of pituitary tumors in laboratory animals. Such studies have been facilitated by the development of newer techniques such as immunocytochemistry and in situ hybridization. Using these methods it has been possible to correlate morphological features with function by characterizing specific pituitary hormones in secretory granules and analyzing the messenger ribonucleic acids produced by specific cell types. Analyses of spontaneous and experimentally induced tumors have provided a great deal of insight into the function and ultrastructure of these neoplasms. The description of tumor cells producing more than one hormone has been facilitated by immunocytochemical analyses. Studies of transgenic models of pituitary hyperplasia and tumor development are expanding our knowledge about the ultrastructure and about other aspects of pituitary tumors in a more controlled experimental setting. The production of various hormones by the same pituitary tumors and even the same tumor cells indicates that complex regulatory mechanisms must be analyzed by a combination of ultrastructural and other techniques to learn more about growth and hormone secretion in pituitary neoplasms.

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Ultrastructure of Pituitary Tumor Cells: A Critical Study

Cited by 30 publications

References 111 publications

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

The Characterization of the Acth Produced by a Primary Pituitary Tumour in a Patient With Cushing's Disease

Structural Correlates of Stimulated and Inhibited Secretion: Electron Microscopic Observations of Somatotrophs in Perifused Rat Pituitary

Ultrastructure of spontaneous and transplanted pituitary tumors in laboratory animals

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